We will be collaborating with centers which are generating genetic expression data on both human tumors and normal tissues to seek candidate proteins suitable for immune attack. Thusfar, we have succeeded in generating and optimizing a chimeric antigen receptor targeting CD70, a protein on nearly all human renal cancer, thymic cancers and many blood cancers and an approved protocol is about to start enrolling. In addition, a mouse T-cell receptor that functions well in human T-cells and recognizes human thyroglobulin as a thyroid cancer antigen has been cloned and a clinical procotol for differentiated thyroid cancer is now open to accrual. Currently we are developing T-cell receptor that immunologically recognize consistently mutated driver mutations common in certain human cancers. Two new TCRs specific for G12D and G12V mutations in RAS have been generated which are restricted by HLA-A11 (15% of the US population and the most common Class I allele in some Asian populations). These are poised to enter clinical trials with T-cell adoptive therapy. New anti-mutRAS receptors with other HLA restrictions are in development.